scholarly journals Extracellular Vesicles and Tumor-Immune Escape: Biological Functions and Clinical Perspectives

2020 ◽  
Vol 21 (7) ◽  
pp. 2286 ◽  
Author(s):  
Stefania Raimondo ◽  
Marzia Pucci ◽  
Riccardo Alessandro ◽  
Simona Fontana
Keyword(s):  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Immune Cell ◽  
Immune Escape ◽  
Immune Checkpoints ◽  
Cancer Therapies ◽  
Biological Functions ◽  
Hallmarks Of Cancer ◽  
Tumor Immune Escape

The modulation of the immune system is one of the hallmarks of cancer. It is now widely described that cancer cells are able to evade the immune response and thus establish immune tolerance. The exploration of the mechanisms underlying this ability of cancer cells has always attracted the scientific community and is the basis for the development of new promising cancer therapies. Recent evidence has highlighted how extracellular vesicles (EVs) represent a mechanism by which cancer cells promote immune escape by inducing phenotypic changes on different immune cell populations. In this review, we will discuss the recent findings on the role of tumor-derived extracellular vesicles (TEVs) in regulating immune checkpoints, focusing on the PD-L1/PD-1 axis.

scholarly journals Cancer associated-fibroblast-derived exosomes in cancer progression

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Chao Li ◽  
Adilson Fonseca Teixeira ◽  
Hong-Jian Zhu ◽  
Peter ten Dijke
Keyword(s):  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Chemotherapy Resistance ◽  
Cell Types ◽  
Cancer Therapies ◽  
Cancer Associated Fibroblast

AbstractTo identify novel cancer therapies, the tumor microenvironment (TME) has received a lot of attention in recent years in particular with the advent of clinical successes achieved by targeting immune checkpoint inhibitors (ICIs). The TME consists of multiple cell types that are embedded in the extracellular matrix (ECM), including immune cells, endothelial cells and cancer associated fibroblasts (CAFs), which communicate with cancer cells and each other during tumor progression. CAFs are a dominant and heterogeneous cell type within the TME with a pivotal role in controlling cancer cell invasion and metastasis, immune evasion, angiogenesis and chemotherapy resistance. CAFs mediate their effects in part by remodeling the ECM and by secreting soluble factors and extracellular vesicles. Exosomes are a subtype of extracellular vesicles (EVs), which contain various biomolecules such as nucleic acids, lipids, and proteins. The biomolecules in exosomes can be transmitted from one to another cell, and thereby affect the behavior of the receiving cell. As exosomes are also present in circulation, their contents can also be explored as biomarkers for the diagnosis and prognosis of cancer patients. In this review, we concentrate on the role of CAFs-derived exosomes in the communication between CAFs and cancer cells and other cells of the TME. First, we introduce the multiple roles of CAFs in tumorigenesis. Thereafter, we discuss the ways CAFs communicate with cancer cells and interplay with other cells of the TME, and focus in particular on the role of exosomes. Then, we elaborate on the mechanisms by which CAFs-derived exosomes contribute to cancer progression, as well as and the clinical impact of exosomes. We conclude by discussing aspects of exosomes that deserve further investigation, including emerging insights into making treatment with immune checkpoint inhibitor blockade more efficient.

scholarly journals MicroRNA-Based Combinatorial Cancer Therapy: Effects of MicroRNAs on the Efficacy of Anti-Cancer Therapies

Cells ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 29 ◽  
Author(s):  
Hyun Ah Seo ◽  
Sokviseth Moeng ◽  
Seokmin Sim ◽  
Hyo Jeong Kuh ◽  
Soo Young Choi ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Combination Therapy ◽  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Therapeutic Resistance ◽  
Cancer Therapies ◽  
Anti Cancer ◽  
Different Types ◽  
Therapeutic Responses

The susceptibility of cancer cells to different types of treatments can be restricted by intrinsic and acquired therapeutic resistance, leading to the failure of cancer regression and remission. To overcome this problem, a combination therapy has been proposed as a fundamental strategy to improve therapeutic responses; however, resistance is still unavoidable. MicroRNA (miRNAs) are associated with cancer therapeutic resistance. The modulation of dysregulated miRNA levels through miRNA-based therapy comprising a replacement or inhibition approach has been proposed to sensitize cancer cells to other anti-cancer therapies. The combination of miRNA-based therapy with other anti-cancer therapies (miRNA-based combinatorial cancer therapy) is attractive, due to the ability of miRNAs to target multiple genes associated with the signaling pathways controlling therapeutic resistance. In this article, we present an overview of recent findings on the role of therapeutic resistance-related miRNAs in different types of cancer. We review the feasibility of utilizing dysregulated miRNAs in cancer cells and extracellular vesicles as potential candidates for miRNA-based combinatorial cancer therapy. We also discuss innate properties of miRNAs that need to be considered for more effective combinatorial cancer therapy.

scholarly journals BTLA-HVEM Couple in Health and Diseases: Insights for Immunotherapy in Lung Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Clemence Demerlé ◽  
Laurent Gorvel ◽  
Daniel Olive
Keyword(s):  
Lung Cancer ◽  
Cancer Progression ◽  
Immune Escape ◽  
Checkpoint Inhibitors ◽  
Immune Checkpoints ◽  
Tumor Immune Escape ◽  
Promising Target ◽  
Tnf Receptor Family ◽  
Receptor Family

Lung cancer is the leading cause of cancer deaths worldwide. Immunotherapies (IT) have been rapidly approved for lung cancer treatment after the spectacular results in melanoma. Responses to the currently used checkpoint inhibitors are strikingly good especially in metastatic diseases. However, durable responses are observed in only 25% of cases. Consequently, there is an urgent need for new immunotherapy targets. Among the multiple checkpoints involved in the tumor immune escape, the BTLA-HVEM couple appears to be a promising target. BTLA (B- and T- Lymphocyte Attenuator) is a co-inhibitory receptor mainly expressed by B and T cells, repressing the activation signal transduction. BTLA shares similarities with other immune checkpoints such as PD-1 and CTLA-4 which are the targets of the currently used immunotherapies. Furthermore, BTLA expression points out terminally exhausted and dysfunctional lymphocytes, and correlates with lung cancer progression. The ligand of BTLA is HVEM (Herpes Virus Entry Mediator) which belongs to the TNF receptor family. Often described as a molecular switch, HVEM is constitutively expressed by many cells, including cells from tumor and healthy tissues. In addition, HVEM seems to be involved in tumor immuno-evasion, especially in lung tumors lacking PD-L1 expression. Here, we propose to review the role of BTLA-HVEM in immuno-escape in order to highlight its potential for designing new immunotherapies.

scholarly journals An Emerging Approach for Combination Therapy of Cancer: The Role of Immunogenic Cell Death

2020 ◽  
Author(s):  
Zahra Asadzadeh ◽  
Elham Safarzadeh ◽  
Sahar Safaei ◽  
Ali Baradaran ◽  
Ali Mohammadi ◽  
...  
Keyword(s):  
Cell Death ◽  
Cancer Cells ◽  
Anticancer Agents ◽  
Immune Escape ◽  
Immunogenic Cell Death ◽  
Cancer Therapies ◽  
Tumor Immune Escape ◽  
Anti Cancer ◽  
Different Types ◽  
Molecular Patterns

Cell death resistance is a key feature of tumor cells. One of the main anti-cancer therapies is increasing the susceptibility of cells to death. Cancer cells have developed a capability of tumor immune escape. Hence, restoring the immunogenicity of cancer cells can be suggested as an effective approach against cancer. Accumulating evidence proposes that several anticancer agents provoke the release of danger-associated molecular patterns (DAMPs) that are determinants of immunogenicity and stimulate immunogenic cell death (ICD). It has been suggested that ICD inducers are two different types according to their various activities. Here, we review the well-characterized DAMPs and focus on the different types of ICD inducers and recent combination therapies that can augment the immunogenicity of cancer cells.

scholarly journals Current Approaches for Combination Therapy of Cancer: The Role of Immunogenic Cell Death

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 1047 ◽  
Author(s):  
Zahra Asadzadeh ◽  
Elham Safarzadeh ◽  
Sahar Safaei ◽  
Ali Baradaran ◽  
Ali Mohammadi ◽  
...  
Keyword(s):  
Cell Death ◽  
Cancer Cells ◽  
Anticancer Agents ◽  
Immune Escape ◽  
Immunogenic Cell Death ◽  
Combination Therapies ◽  
Tumor Immune Escape ◽  
Different Types ◽  
Molecular Patterns

Cell death resistance is a key feature of tumor cells. One of the main anticancer therapies is increasing the susceptibility of cells to death. Cancer cells have developed a capability of tumor immune escape. Hence, restoring the immunogenicity of cancer cells can be suggested as an effective approach against cancer. Accumulating evidence proposes that several anticancer agents provoke the release of danger-associated molecular patterns (DAMPs) that are determinants of immunogenicity and stimulate immunogenic cell death (ICD). It has been suggested that ICD inducers are two different types according to their various activities. Here, we review the well-characterized DAMPs and focus on the different types of ICD inducers and recent combination therapies that can augment the immunogenicity of cancer cells.

scholarly journals Cross-platform meta-analysis reveals common matrisome variation associated with tumor genotypes and immunophenotypes in human cancers

2018 ◽  
Author(s):  
Su Bin Lim ◽  
Swee Jin Tan ◽  
Wan-Teck Lim ◽  
Chwee Teck Lim
Keyword(s):  
Immune Cell ◽  
Immune Escape ◽  
Wide Spectrum ◽  
Meta Analysis ◽  
Immune Checkpoints ◽  
Tumor Immune Escape ◽  
Data Resource ◽  
Specific Tumor ◽  
Cross Platform ◽  
Immune Escape Mechanisms

AbstractBackgroundRecent sequencing efforts unveil genomic landscapes of the tumor microenvironment. Yet, little is known about the extent to which matrisome pattern is conserved in progressive tumors across diverse cancer types, and thus its clinical impact remains largely unexplored.FindingsUsing a newly generated, unified data resource, we conducted cross-platform assessment of a measure of altered extra-cellular matrix (ECM) composition and remodeling associated with tumor progression, termed as the matrisome index (TMI). Parallel analyses with TCGA in over 30,000 patient-derived biopsies revealed that TMI is closely associated with mutational load, tumor histopathology, and predictive of patient outcomes. We found an enrichment of specific tumor-infiltrating immune cell populations, signatures predictive of immunotherapy resistance, and several immune checkpoints in tumors with high TMI, suggesting potential role of ECM interaction with immunophenotyes and tumor immune escape mechanisms. Both epithelial cancer cells and carcinoma-associated fibroblasts are potential cellular contributors of such deregulated matrisome.ConclusionsDespite wide spectrum of genetic heterogeneity and dynamic nature, matrisome abnormalities are integral to disease progression. Our resource of a curated compendium of 8,386 genome-wide profiles, molecular and clinical associations, and matrisome-tumor genotype-immunophenotype relationships identify potentially actionable immune targets that may guide personalized immunotherapy.

scholarly journals Not Only Immune Escape—The Confusing Role of the TRP Metabolic Pathway in Carcinogenesis

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2667
Author(s):  
Iwona Kwiatkowska ◽  
Justyna Magdalena Hermanowicz ◽  
Alicja Przybyszewska-Podstawka ◽  
Dariusz Pawlak
Keyword(s):  
Cancer Cells ◽  
Immune Cell ◽  
Immune Escape ◽  
Kynurenine Pathway ◽  
Cancer Development ◽  
Tumor Promoters ◽  
Direct Impact ◽  
Exact Role ◽  
Cell Functionality

Background: The recently discovered phenomenon that cancer cells can avoid immune response has gained scientists' interest. One of the pathways involved in this process is tryptophan (TRP) metabolism through the kynurenine pathway (KP). Individual components involved in TRP conversion seem to contribute to cancerogenesis both through a direct impact on cancer cells and the modulation of immune cell functionality. Due to this fact, this pathway may serve as a target for immunotherapy and attempts are being made to create novel compounds effective in cancer treatment. However, the results obtained from clinical trials are not satisfactory, which raises questions about the exact role of KP elements in tumorigenesis. An increasing number of experiments reveal that TRP metabolites may either be tumor promoters and suppressors and this is why further research in this field is highly needed. The aim of this study is to present KP as a modulator of cancer development through multiple mechanisms and to point to its ambiguity, which may be a reason for failures in treatment based on the inhibition of tryptophan metabolism

Effect of Annexins Translocated in Extracellular Vesicles on Tumorigenesis

2020 ◽  
Vol 20 ◽  
Author(s):  
Qionghui Wu ◽  
Haidong Wei ◽  
Wenbo Meng ◽  
Xiaodong Xie ◽  
Zhenchang Zhang ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Extracellular Vesicles ◽  
Immune Cell ◽  
Epithelial Mesenchymal Transition ◽  
Main Role ◽  
Tumor Cell Adhesion ◽  
Mesenchymal Transition ◽  
Calcium Dependent ◽  
Tumor Neovascularization

: Annexin, a calcium-dependent phospholipid binding protein, can affect tumor cell adhesion, proliferation, apoptosis, invasion and metastasis, as well as tumor neovascularization in different ways. Recent studies have shown that annexin exists not only as an intracellular protein in tumor cells, but also in different ways to be secret outside the cell as a “crosstalk” tool for tumor cells and tumor microenvironment, thus playing an important role in the development of tumors, such as participating in epithelial-mesenchymal transition, regulating immune cell behavior, promoting neovascularization and so on. The mechanism of annexin secretion in the form of extracellular vesicles and its specific role is still unclear. This paper summarizes the main role of annexin secreted into the extracellular space in the form of extracellular vesicles in tumorigenesis and drug resistance and analyzes its possible mechanism.

Potential of Mesenchymal Stem Cells in Anti-Cancer Therapies

2020 ◽  
Vol 15 (6) ◽  
pp. 482-491 ◽  
Author(s):  
Milena Kostadinova ◽  
Milena Mourdjeva
Keyword(s):  
Cancer Cells ◽  
Small Population ◽  
Tumor Formation ◽  
Bioactive Molecules ◽  
Cancer Therapies ◽  
New Methods ◽  
Cycle Arrest ◽  
Anti Cancer ◽  
Blocking Mechanisms

Mesenchymal stem/stromal cells (MSCs) are localized throughout the adult body as a small population in the stroma of the tissue concerned. In injury, tissue damage, or tumor formation, they are activated and leave their niche to migrate to the site of injury, where they release a plethora of growth factors, cytokines, and other bioactive molecules. With the accumulation of data about the interaction between MSCs and tumor cells, the dualistic role of MSCs remains unclear. However, a large number of studies have demonstrated the natural anti-tumor properties inherent in MSCs, so this is the basis for intensive research for new methods using MSCs as a tool to suppress cancer cell development. This review focuses specifically on advanced approaches in modifying MSCs to become a powerful, precision- targeted tool for killing cancer cells, but not normal healthy cells. Suppression of tumor growth by MSCs can be accomplished by inducing apoptosis or cell cycle arrest, suppressing tumor angiogenesis, or blocking mechanisms mediating metastasis. In addition, the chemosensitivity of cancer cells may be increased so that the dose of the chemotherapeutic agent used could be significantly reduced.

scholarly journals Multifunctional Role of Astrocyte Elevated Gene-1 (AEG-1) in Cancer: Focus on Drug Resistance

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1792
Author(s):  
Debashri Manna ◽  
Devanand Sarkar
Keyword(s):  
Drug Resistance ◽  
Cancer Cells ◽  
Cancer Development ◽  
Epigenetic Alterations ◽  
Hallmarks Of Cancer ◽  
Comprehensive Description ◽  
Molecular Abnormalities ◽  
Selective Pressures ◽  
Resistance To Chemotherapy

Cancer development results from the acquisition of numerous genetic and epigenetic alterations in cancer cells themselves, as well as continuous changes in their microenvironment. The plasticity of cancer cells allows them to continuously adapt to selective pressures brought forth by exogenous environmental stresses, the internal milieu of the tumor and cancer treatment itself. Resistance to treatment, either inherent or acquired after the commencement of treatment, is a major obstacle an oncologist confronts in an endeavor to efficiently manage the disease. Resistance to chemotherapy, chemoresistance, is an important hallmark of aggressive cancers, and driver oncogene-induced signaling pathways and molecular abnormalities create the platform for chemoresistance. The oncogene Astrocyte elevated gene-1/Metadherin (AEG-1/MTDH) is overexpressed in a diverse array of cancers, and its overexpression promotes all the hallmarks of cancer, such as proliferation, invasion, metastasis, angiogenesis and chemoresistance. The present review provides a comprehensive description of the molecular mechanism by which AEG-1 promotes tumorigenesis, with a special emphasis on its ability to regulate chemoresistance.

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